title: Young and older good learners have higher levels of brain nicotinic receptor binding.
abstract: Neuronal alphabeta heteromeric and alpha7 homomeric nicotinic acetylcholine receptors (nAChRs) were compared in 4- and 27-month rabbits selected for learning proficiency. Sixty 4- and 60 27-month rabbits received the alpha7 nAChR agonist (MEM-3389), galantamine, or vehicle during training in trace eyeblink classical conditioning. Brain tissue from the best and worst young and older learners was analyzed with radioligand binding. Vehicle-treated 4- and 27-month good learners had higher alphabeta heteromeric nAChR binding in hippocampus and temporal-parietal cortex than poor learners, and this result was replicated in both age groups of rabbits treated with galantamine. Results indicate that anatomically more numerous nAChRs or functional activation of a greater number of nAChRs may characterize animals demonstrating optimal learning. During normal aging the expression of high-affinity binding sites declines. Age-related changes in the expression of hippocampal alphabeta heteromeric nAChRs may account for some of the documented age-related impairment in learning. However, individual differences in alphabeta heteromeric nAChRs also exist early in life, as better learning in 4-month rabbits was associated with significantly higher binding.
authors.affiliation: Department of Psychology, Temple University, Philadelphia, PA 19122, USA. pak@temple.edu
authors.forename: Diana S
authors.initials: DS
authors.lastname: Woodruff-Pak
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Lehr
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Li
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000157:Aconitine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001767:Blinking / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000493:pharmacokinetics; D005260:Female; D005702:Galantamine / Q000494:pharmacology; D007858:Learning / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D011869:Radioligand Assay / Q000379:methods; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
chemical_list: C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D002800:Cholinesterase Inhibitors; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013141:Spiro Compounds; D005702:Galantamine; D014316:Tritium; C054634:methyllycaconitine; D000109:Acetylcholine; D000157:Aconitine; D004837:Epinephrine